TY - JOUR
T1 - The past, present and future perspectives of matrix metalloproteinase inhibitors
AU - Li, Kang
AU - Tay, Franklin R.
AU - Yiu, Cynthia Kar Yung
N1 - Publisher Copyright:
© 2019
PY - 2020/3
Y1 - 2020/3
N2 - Matrix metalloproteinases (MMPs) are a large family of enzymes that degrade the extracellular matrix (ECM). Under pathologic conditions, overexpression of MMPs or insufficient control by tissue inhibitors of MMPs (TIMPs) results in the dysregulation of tissue remodeling and causes a variety of diseases such as encephalomyelitis, rheumatoid arthritis, Alzheimer's disease and tumors. Therefore, the high affinity of MMPs for biomolecules renders them attractive targets for inhibition when homeostasis breaks down in the ECM. There are 4 generations of MMP inhibitors (MMPIs), ranging from small molecules or peptides to antibodies and protein-engineered inhibitors of metalloproteinase. Although a plethora of MMPIs has been synthesized, most of them have failed in clinical trials or are still in the laboratory stage of development. The present review summarizes the development of MMPIs, their associated problems and discusses future directions for the development of the future generations of MMPIs.
AB - Matrix metalloproteinases (MMPs) are a large family of enzymes that degrade the extracellular matrix (ECM). Under pathologic conditions, overexpression of MMPs or insufficient control by tissue inhibitors of MMPs (TIMPs) results in the dysregulation of tissue remodeling and causes a variety of diseases such as encephalomyelitis, rheumatoid arthritis, Alzheimer's disease and tumors. Therefore, the high affinity of MMPs for biomolecules renders them attractive targets for inhibition when homeostasis breaks down in the ECM. There are 4 generations of MMP inhibitors (MMPIs), ranging from small molecules or peptides to antibodies and protein-engineered inhibitors of metalloproteinase. Although a plethora of MMPIs has been synthesized, most of them have failed in clinical trials or are still in the laboratory stage of development. The present review summarizes the development of MMPIs, their associated problems and discusses future directions for the development of the future generations of MMPIs.
KW - Inhibitor
KW - MMP
KW - MMPI
KW - Matrix metalloproteinase
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U2 - 10.1016/j.pharmthera.2019.107465
DO - 10.1016/j.pharmthera.2019.107465
M3 - Review article
C2 - 31863819
AN - SCOPUS:85076962259
SN - 0163-7258
VL - 207
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
M1 - 107465
ER -